Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

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Baroreflex control of lumbar and renal sympathetic nerve

activity in conscious rats

Roy Kanbar, Bruno Chapuis, Valérie Oréa, Christian Barrès, Claude Julien

Université de Lyon, Lyon, F-69008, France; Université Lyon 1, Lyon, F-69008, France,

Centre National de la Recherche Scientifique FRE 3075

Running head: Baroreflex control of regional sympathetic activities

Corresponding author:

Roy Kanbar

Laboratoire de Physiologie

Faculté de Pharmacie

8, avenue Rockefeller

69373 Lyon Cedex 08, France

Tel.: +33 478 77 70 72

Fax: +33 478 77 71 18

E-mail: [email protected]

of 26Articles in PresS. Am J Physiol Regul Integr Comp Physiol (April 30, 2008). doi:10.1152/ajpregu.00147.2008

Copyright © 2008 by the American Physiological Society.

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ABSTRACT

This study compared the baroreflex control of lumbar and renal sympathetic nerve activity

(SNA) in conscious rats. Arterial pressure (AP), lumbar and renal SNA were simultaneously

recorded in 6 freely behaving rats. Pharmacological estimates of lumbar and renal

sympathetic baroreflex sensitivity (BRS) were obtained by means of the sequential

intravenous administration of sodium nitroprusside and phenylephrine. Sympathetic BRS was

significantly (P < 0.05) lower for lumbar [3.0 +/- 0.4 normalized units (NU)/mmHg] than for

renal (7.6 +/- 0.6 NU/mmHg) SNA. During a 219-min baseline period, spontaneous lumbar

and renal BRS were continuously assessed by computing the gain of the transfer function

relating AP and SNA at heart rate frequency over consecutive 61.4-s periods. The transfer

gain was considered only when coherence between AP and SNA significantly differed from

zero, which was verified in 99 +/- 1 and 96 +/- 3% of cases for lumbar and renal SNA,

respectively. When averaged over the entire baseline period, spontaneous BRS was

significantly (P < 0.05) lower for lumbar (1.3 +/- 0.2 NU/mmHg) than for renal (2.3 +/- 0.3

NU/mmHg) SNA. For both SNAs, spontaneous BRS showed marked fluctuations (variation

coefficients were 26 +/- 2 and 28 +/- 2% for lumbar and renal SNA, respectively). These

fluctuations were positively correlated in 5 of 6 rats (R = 0.44 +/- 0.06; n = 204 +/- 8; P <

0.0001). We conclude that in conscious rats, the baroreflex control of lumbar and renal SNA

shows quantitative differences but is modulated in a mostly coordinated way.

Key words: arterial pressure, baroreceptor reflex, sympathetic nervous system, transfer

function

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INTRODUCTION

The arterial baroreceptor reflex plays a major role in the short-term control of arterial

pressure (AP) mainly through the modulation of efferent sympathetic nerve activity (SNA) to

regional circulations (12). In rats, studies aimed at characterizing the baroreflex control of

SNA under physiological conditions, i.e. in the conscious state, have been based mostly on

recordings of renal SNA (RSNA) (3, 5, 7, 10, 13, 16, 20, 23, 25), mainly because of the

purely postganglionic nature of this activity. Most often, authors implicitly assumed that

RSNA provided a reliable reflection of other regional SNAs. In the meantime, evidence has

accumulated suggesting a differential baroreflex control of regional SNAs in several animal

species (22). In the rat, the comparison of the baroreflex control of regional SNAs has been

carried out in urethane-chloralose anesthetized animals by using the vasoactive drug injection

technique, i.e., the so-called pharmacological method (29, 30). In these studies, it was

reported that the characteristics of the baroreflex function curves differed between RSNA,

lumbar SNA (LSNA) and adrenal SNA. In conscious rats, this information has not been

obtained.

Recently, the concept has emerged that the characteristics of the baroreflex control of

SNA might continuously change as part of normal autonomic responses accompanying

natural behaviors (23), physical exercise (20) and exposure to emotional stress (13). All these

data were obtained using the pharmacological method. Although this method is a valuable

tool to describe the characteristics of the baroreflex function curves, it suffers from some

important limitations. First, a proper use of the method requires stationary conditions, i.e., it

should be applied only when changes in cardiovascular variables have reached a steady state.

Secondly, its temporal resolution is low (several min or tens of min). For these reasons, the

pharmacological method is not suitable for capturing dynamic and short-lasting changes in the

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functional characteristics of the sympathetic baroreceptor reflex. To circumvent these

limitations, we have recently described a new method to assess the renal sympathetic

baroreflex sensitivity (BRS) that does not necessitate the administration of vasoactive drugs.

It is based on the computation of the gain of the transfer function relating RSNA and AP at

heart rate (HR) frequency (24). The method has been validated in partially (aortic)

baroreceptor denervated rats (14). One major advantage of the method is that its temporal

resolution is about 1 min. Therefore, it provides a continuous estimate of sympathetic BRS

and has already been used to show that the renal BRS exhibits minute-to-minute spontaneous

variations (14).

The objective of the present study was to compare the baroreflex control of RSNA and

LSNA in the same conscious rats. The lumbar nerve was chosen because it innervates mainly

the skeletal muscle circulation of the hindlimb (1, 32). The majority of studies performed in

humans are based on recordings of muscle SNA from the peroneal nerve in the leg.

Comparing the baroreflex control of LSNA and RSNA is therefore clinically relevant. LSNA

and RSNA were simultaneously recorded in conscious freely moving rats. Pharmacological

estimates of the sympathetic BRS were obtained by means of the sequential administration of

sodium nitroprusside and phenylephrine (7, 13). Spontaneous renal and lumbar BRS were

assessed with the transfer function method (14).

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METHODS

Animals and surgery. Experiments were performed on 10 to 12 week-old male Sprague-

Dawley rats (Charles River Laboratories, L’Arbresle, France) and were approved by the local

Animal Ethics Committee.

One day before the study, rats (n = 6) were anesthetized with isoflurane (2% in oxygen)

and received an injection of penicillin G (50,000 IU sc). Femoral arterial and venous

polyethylene catheters were then inserted. Four to 6 h later, rats were reanesthetized with

pentobarbital sodium (60 mg/kg iv, supplemented with 10 mg/kg iv as needed) and received

an injection of ketoprofen (5 mg/kg ip). The lumbar chains were accessed through a midline

abdominal incision after gentle retraction of the abdominal aorta and vena cava. One of the

chains was dissected and placed on a bipolar electrode at the L3-L4 level. The nerve-electrode

preparation was embedded in a silicone gel and fixed to the surrounding tissue with alpha-

cyanoacrylate glue, as described by Miki et al. (19). The electrode cable was sutured to the

psoas muscle and guided subcutaneously to exit at the back of neck, at the same site as the

catheters. The abdominal wall was then closed in layers and the rat was turned onto its right

side. Through a flank incision, a branch of the left renal nerve was dissected and a recording

electrode was implanted, as previously described in detail (7, 13, 14). The electrode cable was

also exteriorized at the back of the neck. Both catheter ends and electrode plugs were

protected in a small cap sewn to the skin. Each electrode had a separate ground wire that was

left under the skin. Rats were allowed to recover from anesthesia and surgery during 16 to 18

h in the recording room before starting the study.

Data collection and experimental protocol. AP was measured using a pressure transducer

(TNF-R; Becton Dickinson, Sandy, UT) coupled to an amplifier (model 13-4615-52; Gould,

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Cleveland, OH). Both SNAs were band-pass filtered (300-3,000 Hz) and amplified with a

gain of 100,000 (Model P-511J; Grass, Quincy, MA). AP and SNA signals were sampled at

500 and 10,000 Hz, respectively, by a computer equipped with a 12-bit A/D converter (model

AT-MIO-16; National Instruments, Austin, TX) and LabVIEW 5.0 software (National

Instruments).

After an acclimatization period, AP, LSNA and RSNA were continuously recorded for ~4

h. Thereafter, the baroreflex control of LSNA and RSNA was assessed in awake, resting

animals by means of sequential intravenous injections of sodium nitroprusside (100 µg/kg)

and phenylephrine (50 µg/kg/min for 1 min), as previously described (13). Finally, the mean

level of LSNA and RSNA was recorded after administration of the ganglionic blocker

chlorisondamine (2.5 mg/kg iv). As the lumbar and renal nerves were not cut distal to the

electrode, both remaining SNAs incorporated afferent nerve activity, if present. On

completion of the experiment, rats were euthanized with an intravenous overdose of

pentobarbital sodium and the residual electrical activities were recorded for an additional 20-

min period, which provided estimates of the background noise.

Off-line data analysis. SNA signals were full-wave rectified, low-pass filtered (cut-off

frequency: 150 Hz) and resampled at 5,000 Hz with LabVIEW 6i software. For each SNA,

the corresponding background noise was subtracted from the time series. The spontaneous

sympathetic BRS were calculated as previously described (14). AP, LSNA and RSNA were

resampled at 50 Hz and time series were segmented into 512-points (10.24 s) consecutive data

sets. Coherence and transfer functions were calculated between AP (input signal) and SNA

(output signal) over 11 segments overlapping by half (total duration of 61.4 s) using a fast

Fourier transform algorithm. Autospectra of AP served to locate the frequency at which

maximum power spectral density occurred in the frequency band encompassing HR (usually

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5-8 Hz). For each SNA, coherence, gain and phase were noted at this particular frequency.

Only gain and phase values associated with a significant coherence (0.348 at P < 0.05) (2)

were retained for further calculations. In each rat, the mean of the coherence and transfer gain

and phase were calculated over a 219-min baseline period, which yielded a maximum of 213

values (in case all coherence values were significant). The mean LSNA and RSNA values

were calculated over the same 219-min period and were used as reference values (set to

100%) for normalizing SNA data in spontaneous gain computations.

Pharmacological estimates of the sympathetic BRS were obtained by fitting a sigmoid

function to AP-LSNA and AP-RSNA data pairs collected from the beginning of the

nitroprusside-induced fall in AP up to the maximum phenylephrine-induced rise in AP (7).

This was possible because each SNA followed similar trajectories during the falling and rising

phases of AP, i.e., there was no apparent hysteresis in the sympathetic responses. AP, LSNA

and RSNA time series were resampled at 1Hz by averaging over consecutive 1-s periods. For

each SNA, data were normalized by their respective mean value calculated over the 2-min

period preceding baroreflex testing (set to 100%). A 4-parameter logistic function was then

fitted to AP-SNA data pairs (SigmaPlot 2000, SPSS Inc., Chicago, IL) by an iterative least-

squares procedure: SNA = P1 / {1 + exp[P2(AP-P3)]} + P4, where P1 is the full range of SNA

variation; P2 is a slope coefficient, P3 is AP at half the SNA range; and P4 is the lower plateau

of the curve. From these parameters, the upper plateau (P1 + P4), the threshold AP (P3 – 2/P2),

the saturation AP (P3 + 2/P2) and the operating range (saturation pressure – threshold

pressure) were derived (6, 13). Threshold and saturation AP values lay 11.9 % (of the SNA

range) below and above the upper and lower plateaus, respectively (18). The operating range

indicates the range of AP over which SNA is responsive. The first derivative of the sigmoid

function was computed to determine the baroreflex gain across the full range of AP variation,

including the maximum gain (measured at P3) and the operational gain (measured at the

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reference AP, i.e. the 2-min average value before baroreflex testing). Only the absolute values

of gain are presented.

Statistics. All data are presented as means ± SE. Statistical comparisons were performed

using the Wilcoxon signed rank test.

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RESULTS

Cardiovascular variables. Rats displayed normal behavior, notably eating, drinking,

grooming and resting during the whole recording session. During the 219-min baseline

period, mean values of AP and HR were 109 ± 2 mmHg and 389 ± 13 bpm, respectively. The

mean LSNA and RSNA levels were 4.5 ± 0.8 µV and 1.1 ± 0.3 µV, respectively. After

chlorisondamine administration, the RSNA level did not significantly differ from post-

mortem activity. By contrast, the LSNA level remained 0.39 ± 0.08 µV above post-mortem

activity.

Pharmacological assessment of baroreflex control of regional SNAs. Fig. 1 shows an

example of the reflex responses of LSNA and RSNA to drug-induced changes in AP. The

sigmoid equation could be fitted satisfactorily to each set of AP-SNA data pairs, as indicated

by highly significant, similar coefficients of determination (Fig. 1D and Table 1). Overall,

LSNA appeared less reactive to AP changes than RSNA (Fig. 1). This was reflected in a

lesser maximum reflex sympathoexcitation and a lesser maximum reflex sympathoinhibition

(Fig 2A), which resulted in a range-dependent decrease in the maximum gain for LSNA

compared with RSNA (Fig. 2B and Table 1). The operational gain was also lower for LSNA

than for RSNA. On the other hand, the operating range of baroreflex function curves did not

differ between LSNA and RSNA (Table 1).

Assessment of baroreflex control of regional SNAs by the transfer function method.

Frequency of the AP spectral peak was 6.5 ± 0.2 Hz. At this frequency, coherence between

AP and either SNA was almost always significant (Table 2). These significant coherence

values were usually high (Fig. 3C), so that reliable gain and phase values could be computed.

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The spontaneous index of sympathetic BRS was lower for LSNA than for RSNA (Table 2).

The phase of the transfer function at HR frequency was significantly lower (more negative)

for LSNA than for RSNA (Table 2), suggesting that LSNA lagged behind RSNA by ~20 ms.

Correlation analysis. Both transfer gains showed large variability over time (Fig. 3A).

Variation coefficients were 26 ± 2 and 28 ± 2 % for LSNA and RSNA transfer gain,

respectively. Variations of LSNA and RSNA transfer gain were positively correlated in five

of six rats (R = 0.44 ± 0.06; n = 204 ± 8; P < 0.0001 in all 5 cases) (Fig. 3D). In one rat, the

correlation did not reach significance (R = 0.071; n = 200; P = 0.3161), due to a few outlying

points that were characterized by increases in LSNA transfer gain associated with either no

change or a decrease in RSNA gain. Opposite variations of the transfer gains were sometimes

associated with a slight increase in AP, a decrease in HR, an increase in the LSNA level and a

decrease in the RSNA level. After removing data pairs associated with this particular pattern

of cardiovascular variations (n = 12), the correlation between transfer gains became

significant (R = 0.30; n = 188; P < 0.0001).

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DISCUSSION

In this study, we compared the baroreflex control of lumbar and renal SNA in the same

conscious rats. The pharmacological method provided a description of the entire baroreflex

function curves and demonstrated noticeable differences in some of their characteristics,

especially a range-dependent decrease in lumbar BRS compared with renal BRS. The

spontaneous BRS index derived from transfer function analysis confirmed the decreased

lumbar BRS and allowed extending this observation to most of its spontaneous fluctuations

over time. In most cases, however, these fluctuations were positively correlated with those of

renal BRS, which indicates that the baroreflex control of both regional SNAs is essentially

coordinated.

Methodological issues. Surgery for electrode implantation was performed in two steps.

We did not succeed in chronically implanting both electrodes through a single approach,

either abdominal or retroperitoneal. In addition, the recovery time from surgery was relatively

short when considering the extensive surgery rats underwent. In our hands, the recording of

both SNAs at 24 h post-surgery was possible in about one half of the rats having acutely

recordable signals. This percentage was drastically reduced at 48 h post-surgery.

Notwithstanding these limitations, it should be noted that rats of the present study showed

reasonably low HR values (<400 bpm), which is a good indicator of an acceptable level of

surgical stress, possibly owing to the administration of a long-acting non-steroidal anti-

inflammatory drug before surgery. It is important to note that this class of drugs has been

reported not to impair the baroreceptor sensitivity in rats (28) or the sympathetic BRS in

humans (21).

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The normalization procedure is an important issue that should be considered when

comparing results from different studies. For each SNA, we assigned the value 100% to a

mean level recorded over 219 min under baseline conditions for spontaneous BRS

computation, and during 2 min of rest for pharmacological baroreflex testing. Under these

conditions, any spontaneous or evoked change reflected a variation around the mean. In a

recent study performed on conscious rabbits (27), baroreflex function curves for lumbar and

renal SNA were compared, and the conclusion drawn was that BRS did not differ between the

two SNAs. In this study, the background noise level was taken as the minimum SNA level

observed during phenylephrine infusion, and data were normalized by the maximum value

reached during sodium nitroprusside infusion. Consequently, the SNA range was constrained

to 100 % for both SNAs so that the gain only depended on the slope coefficient P2. In the

present study, it was observed first that phenylephrine was far from eliminating discharges in

LSNA, and secondly that sodium nitroprusside induced much more robust increases in RSNA

than in LSNA (Fig. 1). With the normalization procedure used, the range of SNA variation

was smaller for LSNA than for RSNA, which accorded with the visual inspection of raw data.

As a consequence, and although the slope coefficient P2 did not differ between the two SNAs,

the LSNA gain was markedly lower than the RSNA gain, which is in agreement with previous

studies in anesthetized rats (29, 30).

Physiological issues. SNA was recorded from the lumbar chain at the L3-L4 level

assuming that sympathetic nerves at this level mostly innervate blood vessels in skeletal

muscles of the hindlimb. This assumption is supported by anatomical (1, 32) and functional

(15, 19) studies. In particular, Miki et al. (19) found an inverse relationship between LSNA

and iliac vascular conductance during the various stages of sleep in rats. An inverse

relationship with triceps surae muscle vascular conductance was also found during the early

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stage of fictive locomotion induced by electrical stimulation of the mesencephalic locomotor

region in decerebrate, paralyzed rats (15). However, it should not be ignored that a small

proportion of cutaneous nerve fibers is present in the lumbar chain at this level (11, 31).

Regarding the post- versus preganglionic nature of LSNA, it is of note that the residual LSNA

recorded after ganglionic blockade amounted to almost 10 % of baseline activity, which

would point to a significant contribution from preganglionic axons to overall LSNA, in

accordance with a previous study (29). However, this contribution is probably overestimated

because of the reflex increase in preganglionic SNA that was elicited by the large AP fall

caused by ganglionic blockade. In the present study, it was indeed observed that, after

chlorisondamine administration, residual LSNA could be almost halved by raising AP above

baseline levels with a phenylephrine infusion (data not shown).

Baroreflex control of regional SNAs. LSNA showed a strong rhythmicity at HR frequency

that was strongly correlated to the cardiac beat as shown by the high coherence values

observed between AP and LSNA. These values were comparable to those observed between

AP and RSNA, and thus allowed calculating a reliable spontaneous BRS index for both

SNAs. This method allowed demonstrating that both BRS fluctuate widely over time. These

variations are probably dependent, at least in part, on the behavioral state of the rats (13, 19,

20, 23). Most of the time, spontaneous fluctuations of the renal and lumbar indices of

sympathetic BRS were positively correlated. However, opposite variations were sometimes

observed. This was particularly apparent in one rat that did not show a significant correlation

between the two BRS indices. This was mainly due to outlying points that corresponded to

situations when increases in LSNA gain were associated with decreases in RSNA gain.

During these periods, it was observed that AP slightly increased while HR decreased, LSNA

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slightly increased and RSNA decreased. This particular pattern of cardiovascular changes has

been shown to occur during REM sleep in rats (19, 23).

Both methods for assessing sympathetic baroreflex control revealed a significantly lower

BRS for LSNA than for RSNA, which is in agreement with earlier observations in

anesthetized rats (29, 30). It is known that most, if not all, renal sympathetic nerve fibers are

responsive to the stimulation of arterial baroreceptors (9, 25). On the other hand, the lumbar

sympathetic chain contains a proportion of cutaneous nerve fibers that are poorly

barosensitive (11). It is therefore possible that cutaneous SNA would lower overall BRS

measured at the level of the lumbar chain.

Machado et al. (17) reported that electrical stimulation of the aortic depressor nerve

produces a large reduction in hindlimb vascular resistance with little or no change in renal

vascular resistance, thus suggesting that aortic baroreceptors play a predominant role in the

regulation of hindlimb vascular resistance in rats. This is in apparent disagreement with the

results of the present study which point to a more powerful baroreflex control of RSNA than

of LSNA. Although the reasons for this discrepancy are unclear, it might be suggested that

sympathetic withdrawal is not the sole mechanism of baroreflex vasodilatations in the

hindlimb circulation and that active phenomena are also involved. It has indeed been shown

that the hindlimb circulation of the rat receives a nitroxidergic innervation (8) that might be,

at least partly, under baroreflex control (26). During stimulation of the aortic depressor nerve,

both sympathetic withdrawal and active neurogenic vasodilatation could act in concert,

evoking stronger vasodilatory effects in the hindlimbs than in the kidney.

Relationships between SNA and vascular conductance are not necessarily identical

between different vascular beds, i.e. a given change in SNA will not necessarily result in

identical changes in vascular conductance. Pharmacological studies indicate that the

hindquarter circulation of the conscious rat is less sensitive to the vasoconstrictor effects of

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exogenously administered norepinephrine than the renal circulation (4). It remains, however,

that in conscious rats, both iliac and renal vascular conductance are inversely related to LSNA

and RSNA, respectively (19, 33).

Perspectives and significance. Owing to the simultaneous recording of LSNA and RSNA

in conscious rats, and to the use of pharmacological and spontaneous approaches, we have

shown that the sympathetic BRS is lower when assessed using LSNA than when using

RSNA. In addition, the study shows that renal and lumbar BRS fluctuate widely over time and

that these spontaneous fluctuations are mostly coordinated. The mechanism and physiological

significance of these fluctuations, however, remains to be established. In particular, further

studies are needed to clarify the effect of behavior on the baroreflex control of regional SNAs

and its modulation.

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ACKNOWLEDGEMENTS

This study was partially funded by the French Society of Hypertension.

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FIGURES LEGENDS

Fig 1. Original recordings of AP (A), lumbar (B) and renal (C) SNA during sequential

administration of sodium nitroprusside (SNP) and phenylephrine (PHE) in one conscious rat.

Open traces show mean values averaged over 1 second. D, Baroreflex function curves fitted

to 1-s mean values of SNAs taken from the SNP bolus injection to the end of PHE infusion.

For each SNA, the background noise has been subtracted and data have been normalized by a

reference value calculated over the 2 min preceding baroreflex testing. NU, normalized units;

R², coefficient of determination (observed versus predicted values).

Fig 2. Baroreflex relationships between AP and LSNA and between AP and RSNA

determined under resting conditions in the same conscious rats (n = 6). Group average

parameters were used to generate baroreflex function curves (A) and their first derivative (B).

In A, error bars show SE for the upper and lower plateaus and for AP at midrange of the curve

(P3). The filled circle shows the reference AP-SNA data pair. For both SNAs, the reference

value is equal to 100 normalized units (NU) by definition. In B, filled and open circles show

the maximum and operational (measured at reference AP) gains, respectively.

Fig 3. Example of chronograms of spontaneous indices of lumbar and renal sympathetic BRS.

Transfer function gains (A), phases (B) were computed over 213 adjacent 61.4-s periods. In C,

the horizontal dotted line shows the significance threshold (P < 0.05) for coherence. D, linear

regression analysis between LSNA and RSNA transfer function gains. Note that one value of

RSNA gain was associated with a non significant coherence and thus was eliminated from

further calculations. For each SNA, all gain values were normalized by the corresponding

mean SNA level calculated over the entire recording period.

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Table 1. Characteristics of AP-LSNA and AP-RSNA baroreflex function curves

AP-LSNA AP-RSNA P

Fitted model parameters

R² 0.912 ± 0.022 0.919 ± 0.017 0.4631

P1 (NU) 124 ± 9 329 ± 40 0.0277

P2 (mmHg-1) 0.099 ± 0.010 0.095 ± 0.007 0.4631

P3 (mmHg) 97 ± 1 91 ± 2 0.0277

P4 (NU) 62 ± 5 18 ± 6 0.0277

Derived model parameters

Upper plateau (NU) 186 ± 9 348 ± 37 0.0277

Threshold AP (mmHg) 76 ± 2 69 ± 3 0.1730

Saturation AP (mmHg) 119 ± 3 113 ±1 0.1159

Operating range (mmHg) 43 ± 4 43 ± 3 0.4631

Maximum gain (NU/mmHg) 3.0 ± 0.4 7.6 ± 0.6 0.0277

Operational Gain (NU/mmHg) 2.4 ± 0.3 4.7 ± 0.6 0.0277

Values are means ± SE (n = 6). R², coefficient of determination; P1, RSNA range; P2,

slope coefficient; P3, AP at midrange; P4, lower plateau; NU, normalized units. P values refer

to comparisons between parameters of LSNA and RSNA baroreflex function curves.

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Table 2. Characteristics of AP-LSNA and AP-RSNA coherence and transfer functions at HR

frequency

AP-LSNA AP-RSNA P

Percentage occurrence of

significant coherence values, % 99 ± 1 96 ± 3 0.3430

Mean of significant coherence

values 0.85 ± 0.02 0.81 ± 0.02 0.1730

Transfer function phase, degrees -81 ± 7 -34 ± 3 0.0277

Transfer function gain, NU/mmHg 1.3 ± 0.2 2.3 ± 0.3 0.0277

Values are means ± SE (n = 6). NU, normalized units. P values refer to comparisons

between indices of baroreflex control for LSNA and RSNA.

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AP (mmHg)

40 60 80 100 120 140 160 180

SNA

(N

U)

0

100

200

300

400

500LSNA

RSNA

R² = 0.960

R² = 0.953

0

50

100

150

200

250

20 s

0

20

40

60

0

20

40

60

RSN

A (

µV

)L

SNA

(µ

V)

AP

(m

mH

g)

SNP PHEA

B

C

D

Fig. 1

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SNA

(NU

)

0 20 40 60 80 100 120 140 160 180 2000

100

200

300

400G

ain

(NU

/mm

Hg)

2

4

6

8

10

00 20 40 60 80 100 120 140 160 180 200

A

LSNA

RSNA

AP (mmHg)

B

Fig. 2

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Fig. 3

0

1

2

3

4

0 1 2 3 4

LSNA gain (NU/mmHg)

RSN

A g

ain

(NU

/mm

Hg)

N = 212R = 0.367P < 0.0001

D Time (min)0 55 110 165 220

A

B

C

LSNA

RSNA

0

0.2

0.4

0.6

0.8

1.0

Coh

eren

ce

0

1

2

3

4

Gai

n (N

U/m

mH

g)

-180

-135

-90

-45

0

Pha

se (

degr

ees)

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Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

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